title: Stereodependent inhibition of plasminogen activator inhibitor type 1 by phosphorothioate oligonucleotides: proof of sequence specificity in cell culture and in vivo rat experiments.
abstract: Hexadecadeoxyribonucleotides complementary to a fragment of human PAI-1 mRNA located upstream of the start codon and their phosphorothioate analogs were studied in cultured HUVECs as sequence-dependent inhibitors of PAI-1 expression. The activity of the random mixture of diastereomers of phosphorothioate hexadecanucleotide PS-16H has been compared with that of isosequential, stereoregular [All-Sp] and [All-Rp] isomers. The highest inhibitory effect on PAI-1 synthesis was observed with the [All-Sp] diastereomer. Stereorandom phosphorothioate oligonucleotide PS-16R complementary to the same region of rat PAI-1 mRNA, when injected into tail vein of rats, substantially decreased the level of PAI-1 in blood plasma.
authors.affiliation: Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, Department of Bioorganic Chemistry, Lódź.
authors.forename: W J
authors.initials: WJ
authors.lastname: Stec
authors.forename: C S
authors.initials: CS
authors.lastname: Cierniewski
authors.forename: A
authors.initials: A
authors.lastname: Okruszek
authors.forename: A
authors.initials: A
authors.lastname: Kobylańska
authors.forename: Z
authors.initials: Z
authors.lastname: Pawłowska
authors.forename: M
authors.initials: M
authors.lastname: Koziołkiewicz
authors.forename: E
authors.initials: E
authors.lastname: Pluskota
authors.forename: A
authors.initials: A
authors.lastname: Maciaszek
authors.forename: B
authors.initials: B
authors.lastname: Rebowska
authors.forename: M
authors.initials: M
authors.lastname: Stasiak
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D009943:Organophosphorus Compounds / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013873:Thionucleotides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009943:Organophosphorus Compounds; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013873:Thionucleotides